Argentina might be the best option. It could be the United States of the south. You just need to tie together the mountainous regions of Argentina which have the resources with the great ports and farmlands in the east. And that requires defeating the natives--sadly, they will have to suffer immensely for this to work. It shouldn't really be surprising how Spain conquered all that land--they changed out the native leaders for the Catholic Church hierarchy and above all, the King of Spain. When they met societies that didn't function that way, the results ended in repeated disasters and costly wars at best. This is the case in the North of Mexico, but also in most all of Argentina (plus Southern Chile and interior Paraguay/Bolivia). This is part of the reason why that Buenos Aires (along with much of Eastern Argentina) was so underdeveloped for so long despite the advantageous location. Look at the glacial pace the Argentine frontier pressed south compared to the American frontier. I suspect a lot of this is because of similar weakness of Spanish settlers in New Mexico, but both that and Argentina's case can be alleviated. With stronger bands of settlers pushing on the frontier north and south, and most importantly, far more settlement in Argentina (Spain's immigration policies were too restrictive), you could build a resilient society that can emerge as an independent nation and be a competitor. I think because of the reality of colonisation it'll always be second-tier in the New World to the US, but it can claim a place as a great power as long as you consider a nation like Italy one.
The biggest thing is getting the Chileans onboard with this. Uruguay and Paraguay are both doable as well (they were originally provinces of Argentina anyway), but with Chile, Argentina can gain access to Chile's mineral wealth, which vitally for an industrialising nation, includes some of the few sources of coal on the continent outside of Colombia/Venezuela. The biggest issue happens to be the highest mountain range in the Western Hemisphere lying immediately in the way, which helps to foster an independently-minded state which wouldn't care to listen to what the people on the other side of it want. Clearly Spain thought this way as well, since Chile and Argentina were separate for centuries. If you think of it, its perfectly logical, since aside from going over the Andes, the only other way is to sail around Cape Horn in some of the stormiest seas on the planet. I don't know how to avoid this issue. Perhaps an early Buenos Aires, much more Indian Wars in Argentina, and Spanish settlement at key points in Tierra del Fuego might help. Tying together the Cuyo region at the foot of the Andes and the Buenos Aires area is essential for this to work. Tierra del Fuego could be settled as early as the 17th century--with an early gold rush there, Spain will take note and make it a decent enough place.
The other territorial expansion is in the south of Brazil, and at least Rio Grande do Sul can be claimed for Spain assuming the conflicts with Portuguese settlers and Portugal as a whole go well for them. Since the goal is a strong South American country, I think that's not too hard to do, and would naturally flow from a stronger colonial policy for Spain.
Since we're talking about Argentina, let's hope this changed colonial era butterflies shit like the Argentine Civil Wars. It probably will.
The end result is a powerhouse in the Southern Cone that has some key weaknesses, but is still the second most powerful nation in the Americas and can easily compete with its neighbours like Peru or Brazil.